title: Regulation effects of TZQ-F on adipocyte differentiation and insulin action.
abstract: BACKGROUND
  TZQ has been used in traditional Chineses medicine for treating diabetes. Based on the recipe of traditional anti-diabetic formula TZQ, we have developed TZQ-F which has been in phase 2 clinical trails. To study the mechanisms by which TZQ-F ameliorates diabetes, we examined whether treatment with TZQ-F improves hyperinsulinemia, hyperglycemia and obesity in type 2 diabetic KKA(y) mice and whether this is associated with an improvement of adipocyte differentiation and insulin action.
  
  
  METHODS
  TZQ-F, fenofibrate, rosiglitazone or distilled water was administered to 7-week-old diabetic KKA(y) and nondiabetic C57BL/6J mice for 8 weeks. Insulin resistance index, body weight and levels of serum blood glucose, leptin, insulin and adiponectin were evaluated. The expression of peroxisome proliferator-activated receptor γ (PPARγ) in skeletal muscle and liver tissues were determined with real-time PCR and western boltting. The mRNA expressions of insulin receptor (InsR), insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), glucose transporter-1 (Glut-1) and Phosphoenolpyruvate 3-kinases (PI3K) in skeletal muscle and liver tissues were determined with real-time PCR. Histopathology of liver has been observed.
  
  
  RESULTS
  Treatment of TZQ-F for 8 weeks ameliorated hyperglycemia, hyperinsulinemia, hyperleptinemia and hypoadiponectinemia in KKA(y) mice. TZQ-F also up-regulated expression of PPARγ in liver tissue. However, it had no effect on regulation of expression of PPARγ in muscle tissue. In addition, TZQ-F upregulates InsR, IRS-1, IRS-2, Glut-1, and PI3K mRNA expression. Consistent with the in vivo results, histology study demonstrated that TZQ-F alleviated pathologic changes of the liver induced by high-fat diet.
  
  
  CONCLUSIONS
  These results first indicate that TZQ-F can be beneficial for reducing hyperinsulinemia, hyperglycemia and obesity through its potency of regulating adipocyte differentiation and insulin action.
authors.affiliation: Tianjin University of Traditional Chinese Medicine, #312 Anshanxi Road, Nankai District, Tianjin, 300193, China. Electronic address: xia.jianan@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Nan Xia
authors.forename: De
authors.initials: D
authors.lastname: Qin Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D052242:Adiponectin / Q000097:blood; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D052242:Adiponectin; D019440:Anti-Obesity Agents; D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D047495:PPAR gamma; D012333:RNA, Messenger; C583958:tangzhiqing
keywords: Adiponectin; Insulin resistance; KKA(y) mice; Leptin; Obesity; PPARγ